Huisgen's dipolar cycloaddition of organic azides and alkynes is the most direct route to 1,2,3-triazoles (Huisgen, R. In 1,3-Dipolar Cycloaddition Chemistry; Padwa, A. Ed.; Wiley: New York, 1984). However, because of the high activation energy (ca 24-26 kcal/mol), these cycloadditions are very slow even at elevated temperature and prolonged heating (80-120° C. for 12-24 hours), forming mixtures of regioisomers. The discovery that Cu(I) efficiently and regiospecifically catalyzes cycloadditions of terminal alkynes and azides, providing 1,4-disubstituted 1,2,3-triazoles under mild conditions, was a welcome advance (Rostovtsev, V. V.; et al. Angew. Chem. Int. Ed. 2002, 41, 2596; Tornoe, C. W.; et al. J. Org. Chem. 2002, 67, 3057). The Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC), perhaps the most powerful click reaction (Kolb, H. C.; Sharpless, K. B. Drug Discovery Today, 2003, 8, 1128) to date, has quickly found many applications in chemistry, biology and materials science (Home, W. S.; et al. J. Am. Chem. Soc. 2004, 126, 15366; Manetsch, R.; et al. J. Am. Chem. Soc. 2004, 126, 12809; Link, A. J.; et al. J. Am. Chem. Soc. 2004, 126, 10598; Zhou, Z.; Fahrni, C. J. J. Am. Chem. Soc. 2004, 126, 8862; Lewis, W. G.; et al. J. Am. Chem. Soc. 2004, 126, 9152; Wu, P.; Feldman, A. K.; et al. Angew. Chem., Int. Ed. 2004, 43, 3928; Meng, J. C.; et al. Angew. Chem. Int. Ed. 2004, 43, 1255; Opsteen, J. A.; van Hest, J. C. M. Chem. Commun. 2005, 57; Punna, S.; et al. Angew. Chem. Int. Ed. 2005, 44, 2215).
CuAAC does not afford selective access to the complimentary regioisomers of 1,4-disubstituted 1,2,3-triazoles. Although 1,5-disubstituted triazoles and 1,4,5-trisubstituted triazoles can be synthesized by the reaction of bromomagnesium acetylides with organic azides (Krasinski, A.; Fokin, V. V.; Sharpless, K. B. Org. Lett. 2004, 6, 1237), this method lacks the scope and convenience of the CuAAC process. What is needed is a process for synthesizing 1,5-disubstituted triazoles and 1,4,5-trisubstituted triazoles by a ruthenium-catalyzed “fusion” of organic azides with alkynes.
Catalytic transformations of alkynes mediated by ruthenium complexes are well known, and evidence for the intermediacy of ruthenium (II) acetylide, vinylidene and ruthenametallacyclic complexes has been provided (Naota, T.; et al. Chem. Rev. 1998, 98, 2599; Bruneau, C.; Dixneuf, P. H. Acc. Chem. Res. 1999, 32, 311; Trost, B. M.; et al. Chem. Rev. 2001, 101, 2067). What is needed is ruthenium complexes employable in azide-alkyne cycloaddition reactions.